The main objectives of this project are to: (1) examine formation, release, metabolism and disposition of brain biogenic amines and their alterations after administration of drugs or toxin~induced models of human disease; (2) determine the physiologic role of biogenic amines in mediating responses to stress; and (3) develop methods that can be adapted to study of brain biogenic amine metabolism in humans. In vivo microdialysis has been used to monitor levels of monoamines and their metabolites in extracellular fluid in various regions of the hypothalamus and in the basal ganglia. Receptors and trans~porters have been examined in vitro using cells from different regions of brain: in cell lines cultured from the hypothalamus. Results of studies using microdialysis have shown that norepinephrine (NE) release in the paraventricular nucleus (PVN) varies with the stressor, being greatest with immobilization and least with hypoglycemia. Furthermore, by unilateral interruption of ascending noradrenergic pathways in the brain stem, the degree of innervation of the hypothalamic nuclei can be assessed. Locally administered glycine, intro~duced into the regions of the tip of a microdialysis probe, elicits dose~dependent, strychnine~sensitive dopamine release. The interaction of glycine with nicotinic acetylcholine receptors in bovine adrenal medullary membranes (demonstrated in vitro by NMR) suggests that the amino acid modulates this receptor at one of two sites whichare strychnine sensitive. Endogenous serotonin also appears to influence pamine release from the striatum.